Effects of MEK1/2 blocker U0126 on the medial preoptic synapse and behavioral selection of male mice

The central part of the mouse medial preoptic area (cMPOA) is involved in parental behavior because the neurotoxic lesion of the cMPOA disturbed parental behavior and switched to infanticidal behavior. The cMPOA receives projection from many brain regions, including the medial amygdala (Me). We have previously found that optogenetic inhibition of the projection pathway from the Me to the cMPOA in virgin male mice suppressed the infanticidal behavior of virgin mice toward pups. Furthermore, electrophysiological analysis has revealed that intracellular signaling-mediated disinhibition occurs in the cMPOA neurons during the transition from virgin to father in gestation experience (FGE) mice. However, the specific downstream signal transduction pathway remains unclear. In this study, we utilized U0126, a MEK1/2 inhibitor, because U0126 has been reported to modulate GABAergic currents. Therefore, we examined the contribution of U0126 at the synaptic and behavioral levels. Applying U0126 to the cMPOA neurons in FGE mice restored eIPSP as much as that in cMPOA neurons in virgin mice. Furthermore, microinfusion of U0126 into the cMPOA shifted the behavioral pattern of FGE mice toward infanticide. These changes were not observed in the mice that experienced parenting. The results suggest that MEK1/2 mediates neurotransmission in the cMPOA and contributes to the stage transition from virgin to FGE mice after mating with females.